TY - JOUR
T1 - Activation of the cardiac ATP-sensitive K+ channel by ER-001533, a newly synthesized vasorelaxant
AU - Shen, Win K.
AU - Tung, Robert T.
AU - Kurachi, Yoshihisa
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1992/5
Y1 - 1992/5
N2 - Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the whole-cell" and "inside-out" patch configurations. In the whole-cell clamp condition, ER induced a time-independent K+-dominant current, which was inhibited by glibenclamide (1-3 μM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (KATP). To elucidate the mechanism of ER-mediated KATP channel activation, the drug was applied to the inside-out patches before and after channel "run-down." Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the KATP channel only in the presence of ATP. ER shifted the relation between [ATP]i and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slope. After channel run-down, ER did not affect the channel openings either in the absence or in the presence of UDP. However, ER could relieve the ATP-γ-S inhibition of the UDP-induced channel openings. Thus, we conclude that ER antagonizes the inhibitory effect of ATP on the KATP channel in a competitive manner, thereby enhancing the channel openings. (Circulation Research 1992;70:1054-1061).
AB - Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the whole-cell" and "inside-out" patch configurations. In the whole-cell clamp condition, ER induced a time-independent K+-dominant current, which was inhibited by glibenclamide (1-3 μM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (KATP). To elucidate the mechanism of ER-mediated KATP channel activation, the drug was applied to the inside-out patches before and after channel "run-down." Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the KATP channel only in the presence of ATP. ER shifted the relation between [ATP]i and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slope. After channel run-down, ER did not affect the channel openings either in the absence or in the presence of UDP. However, ER could relieve the ATP-γ-S inhibition of the UDP-induced channel openings. Thus, we conclude that ER antagonizes the inhibitory effect of ATP on the KATP channel in a competitive manner, thereby enhancing the channel openings. (Circulation Research 1992;70:1054-1061).
KW - ATP-sensitive K channel
KW - Cardiac myocytes
KW - ER-001533
UR - http://www.scopus.com/inward/record.url?scp=0026561501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026561501&partnerID=8YFLogxK
M3 - Article
C2 - 1568297
AN - SCOPUS:0026561501
SN - 0009-7330
VL - 70
SP - 1054
EP - 1061
JO - Circulation research
JF - Circulation research
IS - 5
ER -